Early predictors of two month response with mianserin and selective serotonin reuptake inhibitors and influence of definition of outcome on prediction.

In order to identify clinical and demographic variables that predict response to antidepressants and to analyse prediction of outcome as a function of definition of outcome we analysed pooled data of two independent, multicentre, double blind parallel group studies. Study I compared the efficacy of mianserin with that of fluoxetine in 65, and study II compared mianserin with fluvoxamine in 60 patients with depression. Improvement was defined as at least 20% decrease in MADRS by day 14. Patients were considered as responders if they had greater than 50% decrease and non-responders if they had </= 50% decrease from baseline in the MADRS at day 56. Complete remission was defined as MADRS score </= 6 at day 56. Patients' characteristics did not differ between mianserin and SSRI groups. Early improvement predicted response in 92% and complete remission in 55% of the patients improved at day 14. Multivariate forward stepwise logistic regression analysis showed that response to treatments at day 56 was significantly (P = 0.0003) associated with early improvement, age (responders had higher age than non-responders) and weight (responders weighted more than non-responders). Complete remission was only predicted by early improvement. Treatments could not be differentiated when data were analysed according to responder/nonresponder status or complete remission/no complete remission. However, when the same data were analysed by analysis of variance a significant treatment effect (P = 0.02, mianserin > SSRIs) and a quadratic type treatment by time interaction (P = 0.023) were found. The robustness of the analysis was further improved by inclusion of covariates (age, weight). Early clinical improvement seems to be the best predictor of 2 month response to antidepressants (mianserin, SSRIs). Younger age and lower weight may predict non-response. Quantitative analysis differentiates treatments better than analysis of responder status. As obtenation of complete remission is a realistic objective with current antidepressants, studies longer than 2 months are needed to assess effectiveness of these drugs in the obtenation of complete remission.

RCT Entities:   Population Interventions Outcomes